This invention relates to delivery of a therapeutic agent to a region of interest using a contrast agent and activation of the therapeutic agent using ultrasound energy and, more particularly, to methods and apparatus for displaying information relating to delivery and activation of the therapeutic agent.
Ultrasound imaging is widely used in diagnostic medical applications to non-invasively observe structures within the human body, such as cardiac structures, the vascular system, the fetus, the uterus, the abdominal organs and the eye. In a typical imaging system, short bursts of ultrasound energy are directed into a patient""s body with a handheld transducer. The returning reflected energy is received by the same transducer, and signals representing the reflected energy are processed and formatted into a video image of the target region. Phased-array scanning techniques are commonly used.
Current trends in research involve investigations of non-linear responses to, ultrasound energy. For example, some contrast agents have been found to provide a harmonic response to ultrasound energy. This response can be used to provide increased diagnostic information about the tissue in a region of interest. Many contrast agents demonstrate tissue perfusion when administered through intravenous injection. The contrast agents are often configured as microbubbles that comprise a shell which acts to contain an internal gas or other contrast enhancing agent. For instance, perfluorocarbon-exposed sonicated dextrose albumin microbubbles have been employed to improve the contrast of ultrasound images. Typically, these microbubbles can be destroyed if sufficiently high levels of ultrasonic energy are applied. Diagnostic ultrasound imaging with contrast agents is disclosed in U.S. Pat. Nos. 5,833,613 issued Nov. 10, 1998 to Averkiou et al; U.S. Pat. No. 5,740,128 issued Apr. 14, 1998 to Hossack et al; U.S. Pat. No. 5,255,683 issued Oct. 26, 1993 to Monaghan; U.S. Pat. No. 5,456,257 issued Oct. 10, 1995 to Johnson et al; U.S. Pat. No. 5,577,505 issued Nov. 26, 1996 to BrockFisher et al; and U.S. Pat. No. 5,706,819 issued Jan. 13, 1998 to Hwang et al, and in European Patent Application No. EP 0 851 241 published Jul. 1, 1998.
Ultrasound systems may also be utilized in connection with the targeted delivery of a therapeutic agent, such as a drug or a gene, to a region of interest. The therapeutic agent is encapsulated in or is otherwise attached to microbubbles of a contrast agent. The contrast agent containing the therapeutic agent is administered to a region of interest in a patient, and ultrasound energy is applied to the region of interest, causing destruction of the microbubbles, and release, or activation, of the therapeutic agent. This technique is disclosed, for example, in U.S. Pat. No. 5,558,092 issued Sep. 24, 1996 to Unger et al.
The delivery and activation of a therapeutic agent in this manner must be controlled in order to ensure proper dosage. Accordingly, there is a need for measurement and display techniques which facilitate control of the process.
According to a first aspect of the invention, a method is provided for administering a therapeutic agent, such as a drug or a gene, to a patient. The method comprises the steps of delivering a therapeutic agent to a region of interest, generating an ultrasound image of the region of interest, transmitting ultrasound energy to the region of interest for activating the therapeutic agent, and generating a parameter display that is indicative of activation of the therapeutic agent in the region of interest.
Preferably, the therapeutic agent is incorporated into microbubbles of a contrast agent, and the microbubbles containing the therapeutic agent are delivered to the region of interest. The transmitted ultrasound energy activates the therapeutic agent by destroying the microbubbles of the contrast agent and releasing the therapeutic agent.
The method may further include the step of adjusting one or more parameters of the ultrasound energy transmitted to the region of interest. The parameters of the transmitted ultrasound energy may be adjusted manually based on the parameter display or may be adjusted automatically based on acquired parameter data, such as a measurement of microbubble destruction in the region of interest. The parameter display thus provides feedback for control of the activation process.
In one approach, the parameter display may represent a parameter, such as ultrasound transmit power, ultrasound transmit frequency, ultrasound pressure or ultrasound mechanical index, of the ultrasound energy applied to the region of interest. In another approach, the parameter display may be generated by detecting microbubble destruction, and generating a display that is indicative of microbubble destruction in the region of interest.
In a first embodiment, the parameter display may comprise a colorized display. In one example, specified colors are indicative of cumulative dose of the therapeutic agent delivered to the region of interest. In another example, specified colors are indicative of parameter values or ranges of values associated with activating the therapeutic agent. In a second embodiment, the parameter display may comprise a graphical representation of a parameter that is indicative of activation of the therapeutic agent as a function of time or a spatial parameter. For example, the graphical representation may comprise a graph of cumulative dose of the therapeutic agent as a function of time. In a third embodiment, the parameter display may comprise an area display that overlays the ultrasound image and is indicative of the spatial distribution of a parameter. For example, the area display may show contours of constant value of a parameter.
According to another aspect of the invention, apparatus is provided for facilitating administration of a therapeutic agent to a patient. The therapeutic agent is incorporated into microbubbles of a contrast agent and is delivered with the contrast agent to a region of interest in the patient. The apparatus comprises means for generating an ultrasound image of the region of interest, means for transmitting ultrasound energy to the region of interest for destroying the microbubbles of the contrast agent, means for acquiring parameter data that is representative of destruction of the microbubbles of the contrast agent and means for generating a parameter display of the acquired parameter data. The parameter display is indicative of activation of the therapeutic agent in the region of interest.
According to a further aspect of the invention, a method is provided for administering a therapeutic agent to a patient. The method comprises the steps of delivering to a region of interest in a patient a therapeutic agent that is incorporated into microbubbles of a contrast agent, generating an ultrasound image of a region of interest, transmitting ultrasound energy to the region of interest for destroying the microbubbles of the contrast agent, acquiring parameter data that is indicative of activation of the therapeutic agent, and automatically adjusting one or more parameters of the ultrasound energy transmitted to the region of interest, based on the acquired parameter data.